Summary
CPT-11 is a prodrug activated by carboxylesterases to the active metabolite SN-38 which is a potent inhibitor of topoisomerase I. CPT-11 is of clinical interest in the treatment of colorectal cancer. We evaluated the activities of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo I) in 53 colorectal tumours, in eight liver metastases and in normal tissue adjacent to the tumours. Both CPT-CE and topo I activities were widely variable in the malignant and the normal tissue of patients with colorectal carcinomas. CPT-CE was only two to threefold lower in primary tumours compared to normal liver, suggesting that a local conversion to SN-38 might occur in tumour cells. CPT-CE was similar in liver and in normal colon tissues. Levels of topo I in tumour ranged from 580 to 84 900 U mg protein–1 and was above 40 000 U mg protein–1 in 11 of 53 patients. Similarly, a very high ratio (> 5) between tumour and normal tissues were observed in 12 of 53 patients. An inverse correlation was observed between the topo I activity and the clinical stage of disease. Clinical studies are in progress in our institution to explore a possible relationship between CPT-CE and topo I activities in tumour cells and the response to CPT-11-based chemotherapy in patients with colorectal cancer.
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16 November 2011
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Guichard, S., Terret, C., Hennebelle, I. et al. CPT-11 converting carboxylesterase and topoisomerase I activities in tumour and normal colon and liver tissues. Br J Cancer 80, 364–370 (1999). https://doi.org/10.1038/sj.bjc.6690364
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DOI: https://doi.org/10.1038/sj.bjc.6690364
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